Author + information
- Devyani Chowdhurya,b,
- Christine Pascuaa,b,
- Millie Younga,b,
- Michael Horsta,b,
- Michael A. McCullocha,b,
- Samuel Giddinga,b,
- Erik Puffenbergera,b,
- Kevin Straussa,b and
- Katie Williamsa,b
Background: Familial hypercholesterolemia (FH) due to APOB c.10580G>A (p.Arg3500Gln) is associated with elevated low-density lipoprotein (LDL) and accelerated atherosclerosis in adults. The pediatric phenotype has not been described.
Methods: Five Old Order Amish families with APOB c.10580G>A were identified. The cohort consisted of 13 heterozygotes (14±8 yrs), 3 homozygotes (12±9 yrs), and 9 unaffected age-matched sibling controls (15±6 yrs). Mobile equipment was used to measure carotid intima media thickness (CIMT), pulse wave velocity, and reactive hyperemia in home environments following an overnight fast.
Results: LDL cholesterol was elevated in APOB c.10580G>A heterozygotes (167 ± 40 mg/dL, p=0.002) and homozygotes (311 ± 27 mg/dL, p<0.0001) relative to age-matched sibling controls (LDL 100 ± 33 mg/dL). There was overlap in LDL levels among the heterozygotes and controls. Among the heterozygote 5 (38%) had LDL ≤ 160 mg/dL, 3 (23%) had LDL 160-190 mg/dL and 5 (38%) had LDL 190 −220 mg/dL; all homozygotes had LDL levels >280 mg/dL. (fig1) Serum LDL did not correlate with imaging parameters or age, but CIMT increased with age among the heterozygotes (rs=0.78, p=0.006). (fig2)
Conclusions: In patients with APOB c.10580G>A LDL levels are lower than other genotypes causing FH. Conventional measures of vascular function are of uncertain clinical value among pediatric subjects, but CIMT data indicate that young APOB c.10580G>A heterozygotes might have accelerated atherosclerosis independent of LDL.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Advances in Cholesterol Measurement and Management
Abstract Category: 32. Prevention: Clinical
Presentation Number: 1106-070
- 2017 American College of Cardiology Foundation